5.33060

HMGB Inhibitor, Inflachromene

• Synonym(s): HMGB Inhibitor, Inflachromene, Neuroinflammatory Inhibitor, Inflachromene, HMGB2 Inhibitor, Inflachromene, 10-Hydroxy-7,7-dimethyl-2-phenyl-7,12b-dihydrochromeno[4,3-c][1,2,4]triazolo[1,2-a]pyridazine-1,3(2H,5H)-dione
• Empirical Formula (Hill Notation): C₂₁H₁₉N₃O₄
• Molecular Weight: 377.39
• UNSPSC Code: 12352200
• PubChem Substance ID: 49857340

Properties

• assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C
• SMILES string: CC1(C2=CCN3C(=O)N(C(=O)N3C2C4=C(O1)C=C(C=C4)O)C5=CC=CC=C5)C

Description

General description

A cell-permeable, chromene-fused benzopyran-embedded tetracyclic compound that selectively and directly binds to the DNA binding domain box A of high mobility group box (HMGB) proteins and blocks their post-translational phosphorylation and acetylation. Diminishes the cytoplasmic accumulation of HMGB2 in microglial cells. Blocks lipopolysaccharide (LPS)-induced nitrite release in BV-2 microglial cells, RAW 264.7 macrophages, and mouse primary microglial cultures (~50 nM to 20 µM) without inducing any toxicity. However, it is shown to be less potent in primary astrocytes. Suppresses LPS-stimulated increase in the levels of IL-6, IL-1b, NOS2, and TNFα genes and inhibits the nuclear translocation of NF-κB. Also shown to reduce LPS-induced phosphorylation of ERK, JNK, and p38 MAP kinases in microglia. Reduces neuroinflammation, neurite damage, and spinal cord demyelination in a murine model of auto-immune encephalitis (~10 mg/kg).

A cell-permeable, chromene-fused benzopyran-embedded tetracyclic compound that selectively and directly binds to the DNA binding domain box A of high mobility group box (HMGB) proteins and blocks their post-translational phosphorylation and acetylation. Diminishes the cytoplasmic accumulation of HMGB2 in microglial cells. Blocks lipopolysaccharide (LPS)-induced nitrite release in BV-2 microglial cells, RAW 264.7 macrophages, and mouse primary microglial cultures (~50 nM to 20 µM) without inducing any toxicity. However, it is shown to be less potent in primary astrocytes. Suppresses LPS-stimulated increase in the levels of IL-6, IL-1b, NOS2, and TNFα genes and inhibits the nuclear translocation of NF-κB. Also shown to reduce LPS-induced phosphorylation of ERK, JNK, and p38 MAP kinases in microglia. Reduces neuroinflammation, neurite damage, and spinal cord demyelination in a murine model of auto-immune encephalitis (~10 mg/kg).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
HMGB2

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Lee, S., et al. 2014. Nat. Chem. Biol.10, in press.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable